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CALCIUM AND

PHOSPHATE
METABOLISM
PRESENTED BY –
DR.HARIPRASAD L
1ST YEAR MDS.
CONTENTS.
 INTRODUCTION
 CALCIUM METABOLISM.
BIOCHEMICAL FUNCTIONS
SOURCES AND DIETARY REQUIREMENTS.
ABSORPTION
PLASMA CALCIUM
EXCRETION OF CALCIUM
DISEASE STATES
CONTENTS.
 PHOSPHORUS METABOLISM.
BIOCHEMICAL FUNCTIONS
DIETARY REQUIREMENTS AND SOURCES
ABSORPTION
SERUM PHOSPHATE
EXCRETION
DISEASE STATES
INTRODUCTION
 The mineral elements constitute only a small proportion
of the body weight.

 There is a wide variation in their body content. For


instance, calcium constitutes about 2% of body weight
while cobalt about 0.00004%.

0.00004%
2% ca
Co
GENERAL FUNCTIONS:
 Minerals perform several vital functions which are absolutely essential
for the very existence of the organism.
 These include calcification of bone, blood coagulation, neuromuscular
irritability, acid-base equilibrium, fluid balance and osmotic
regulation.
CLASSIFICATION
MINERALS

Principal elements Trace elements


(Less than 100 mg/day)
a) Essential trace elements
b) Possibly essential elements
c) Non essential trace elements
TRACE ELEMENTS:

Essential trace elements:


Iron, copper, iodine, manganese/ zinc, molybdenum, cobalt,
fluorine, selenium and chromium.

Possibly essential elements:


Nickel, vanadium, cadmium and barium.

Non essential trace elements:


Aluminium, lead, mercury, boron, silver, bismuth.
CALCIUM

 Calcium is the most abundant among the minerals in the body.

 The total content of calcium in an adult man is about 1 to 1 .5


kg. As much as 99% of it is present in the bones and teeth.

 A small fraction (1%) of the calcium, found outside the skeletal


tissue, performs a wide variety of functions.

1%

Skeletal
Non skeletal
99%
BIOCHEMICAL FUNCTION OF CALCIUM:

1. Development of bones and teeth :


 Calcium, along with phosphate, is required for the
formation of hydroxyapatite and physical strength of
skeletal tissue.
 Bone is regarded as a mineralized connective tissue and
Bones which are in a dynamic state serve as reservoir of
Ca.
2. Muscle contraction:
 Ca2+ interacts with troponin C to trigger muscle contraction.
 Calcium also activates ATPase, increases the interaction between actin
and myosin.
3. Blood coagulation :
 Several reactions in the cascade of blood clotting process
are dependent on Ca2+.
4. Nerve transmission:
Ca2+ is necessary for the transmission of nerve impulse.
5. Membrane integrity and permeability :

Ca2+ influences the membrane structure and transport of


water and several ions across it.

6. Activation of enzymes :

Ca2+ is needed for the direct activation of enzymes such as


lipase, ATPase and succinate dehydrogenase.
7. Calmodulin mediated action of Ca2+ :
Calmodulin is a calcium binding regulatory protein. Ca-calmodulin
complex activates certain enzymes.
e.g. adenylate cyclase, Ca2+ dependent protein kinases.
8. Calcium as intracellular messenger :
Certain hormones exert their action through the mediation of
Ca2+
 Calcium is regarded as a second messenger for such
hormonal action.
e.g. epinephrine.
 Calcium serves as a third messenger for some hormones.
e.g. antidiuretic hormone (ADH) acts through cAMP, and then
ca2+.
9. Release of hormones :
The release of certain hormones from the endocrine glands is
facilitated by Ca2+.

10. Secretory processes :


Ca2+ regulates microfilament and microtubule mediated
processes such as endocytosis, exocytosis and cell motility.
11. Contact inhibition :
Calcium is believed to be involved in cell to cell contact and
adhesion of cells in a tissue. The cell to cell communication
may also require ca 2+.

12. Action on heart :


Ca2+ acts on myocardium and prolongs systole
ON ORAL STRUCTURES.
 Mineralised tooth:
 Pre-eruptive effects of calcium:

 On geriatric patients:

“What is good for oral cavity is good for body.”


 Periodontium:
DIETARY REQUIREMENTS:

• Adult men and women - 800 mg/day


• Women during pregnancy/
lactation and post-menopause - 1.5 g/day
• Children (1-18 yrs.) - o.8-1.2 g/day
• Infants (below 1 yr) - 300-500 mg/day
SOURCES:
Best sources - Milk and milk products
Good sources - Beans, leafy vegetables, fish, cabbage, egg yolk.
ABSORPTION:
The absorption of calcium mostly occurs in the duodenum by
an energy dependent active process.

FACTORS PROMOTING CALCIUM ABSORPTION:


 Vitamin D induces the synthesis of calcium binding protein
in the intestinal epithelial cells and promotes Ca
absorption.
 Parathyroid hormone enhances Ca absorption through the
increased synthesis of calcitriol.

 Acidity (low pH) is more favourable for Ca absorption.

 Lactose promotes calcium uptake by intestinal cells.

 The amino acids lysine and arginine facilitate Ca


absorption.
FACTORS INHIBITING CALCIUM ABSORPTION:

 Phytates and oxalates form insoluble salts and interfere


with Ca2+ absorption.

 High content of dietary phosphate results in the formation


of insoluble calcium phosphate and prevents Ca2+ uptake.
 The free fatty acids react with Ca to form insoluble calcium
soaps. This is particularly observed when the fat absorption is
impaired.

 Alkaline condition is unfavourable for Ca absorption.

 High content of dietary fiber interferes with Ca absorption.


PLASMA CALCIUM

 Most of the blood Ca is present in the plasma since the


blood cells contain very little of it.

 The normal concentration of plasma or serum Ca is 9-11


mg/dl.
FACTORS REGULATING PLASMA CALCIUM LEVEL:

 The hormones responsible for the HOMEOSTASIS of calcium


are :

* CALCITRIOL

* PARATHYROID HORMONE

* CALCITONIN
1. CALCITRIOL:
 Is the physiologically active form of vitamin D.

INTESTINE:
CALCITRIOL
(induces)
SPECIFIC CALCIUM BINDING PROTEIN

INCREASES THE CALCIUM AND PHOSPHATE ABSORPTION


BONES

CALCITRIOL

CALCIUM UPTAKE BY OSTEOBLASTS

MINERALISATION/CALCIFICATION OF BONES

REMODELLING
2. PARATHYROID HORMONES:
 lt is originally synthesized as prepro PTH which is degraded to
pro-PTH and finally, to active PTH.

 The rate of formation and the secretion of PTH are promoted


by low Ca2+ concentration.
Action on the bone:
PTH causes decalcification or demineralization of bone, a process
carried out by osteoclasts.

PTH secretion

Release of pyrophosphatase and collagenase

Increased activity of Osteoclasts

Demineralisation of bones

Increased serum calcium


Action on the kidney:
 PTH increases the Ca reabsorption by kidney tubules. This is the most rapid
action of PTH to elevate blood Ca levels.
 PTH promotes the production of calcitriol in the kidney by stimulating
hydroxylation of 1,25-hydroxycholecalciferol.

Action on the intestine :


 The action of PTH on the intestine is indirect.
 It increases the intestinal absorption of Ca by promoting the synthesis of
calcitriol.
CALCITONIN(CT):

 Calcitonin is a peptide containing 32 amino acids.


 The action of CT on calcium metabolism is antagonistic to
that of PTH, hence aids in mineralizing bone with osteoblastic
activity.
 Calcitonin decreases bone resorption and increases the
excretion of Ca into urine.
 Therefore Calcitonin has a decreasing influence on blood
calcium.
Importance of Ca : P ratio;

 The ratio of plasma Ca : P is important for calcification of


bones.

 The product of Ca x P (in mg/dl) in children is around 50


and in adults around 40.

 This product is less than 30 in rickets.


Excretion of calcium:

 Calcium is excreted partly through the kidneys and mostly


through the intestine.

 The renal threshold for serum Ca is 10 mg/dl.

 Ingestion of excess protein causes increased calcium excretion


in urine.

 Excretion of Ca into the feces is a continuous process and this is


increased in vitamin D deficiency.
DISEASE STATES

 The blood Ca level is maintained within a narrow range by


the homeostatic control, most predominantly by PTH.

 Hence abnormalities in Ca metabolism are mainly


associated with alterations in PTH.
Hypercalcemia:
 Elevation in serum Ca level is hypercalcemia (upto 10-
15mg/dl).
 Hypercalcemia is associated with hyperparathyroidism caused
by increased activity of parathyroid glands.
 Elevation in the urinary excretion of Ca and P, often resulting
in the formation of urinary calculi.
The determination of ionized serum calcium (elevated to 6-9mg/dl)
is more useful for the diagnosis of hyperparathyroidism.

Symptoms of Hypercalcemia:
 Lethargy

 Muscle weakness
 Loss of appetite

 Constipation

 Nausea

 Increased myocardial contractility

 Susceptibility to fractures
HYPOCALCEMIA:
 It is characterized by a fall in the serum Ca to below 7
Mg/dl, causing tetany.
 Hypocalcemia is mostly due to hypoparathyroidism, which
may happen after accidental removal of parathyroid
glands.
TROUSSEAU’S
SIGN

CHVOSTEK SIGN
Symptoms:

 Neuromuscular irritability
 Spasms
 Cramps
 Muscle weakness
 Convulsion
 Sensations of piercing with pins.
MANAGEMENT OF HYPOCALCEMIA:

 Calcium gluconate 10ml -10% diluted in 50ml of 5%


dextrose and 0.9% Nacl by slow injection.

 Vitamin D – if hypocalcaemia persist.


RICKETS:
 Rickets is a disorder of defective calcification of bones.

 This may be due to a low levels of vitamin D in the body or


due to a dietary deficiency of Ca and P or both.

 An increase in the activity of alkaline phosphatase is a


characteristic feature of rickets.
RENAL RICKETS:

 Renal rickets is associated with damage to renal tissue,


causing impairment in the synthesis of calcitriol.

 It does not respond to vitamin D in ordinary doses,


therefore it is regarded as vitamin D resistant rickets.

 It can be treated by administration of calcitriol.


Oral Manifestations:
 Developmental abnormalities of dentin and enamel.

 Delayed eruption.

 Misalignment of teeth in the jaw.

 High caries index.

 Enamel hypoplasia.
OSTEOPOROSIS:
 Osteoporosis is characterized by demineraIization of bone
resulting in the progressive loss of bone mass.

 Occurance: High in elderely person of both sexes(above 60


years) and post menopausal women.

 It is regarded as silent thief as it is responsible for


majority of the disability due to frequent bone loss among
the old age group.
Etiology: The etiology of osteoporosis is largely unknown.
But several causative factors may contribute to it.

 The ability to produce calcitriol from vitamin D is


decreased with age and particularly in the
postmenopausal women.

 Deficiency of sex hormones in women has been implicated


in the development of osteoporosis.
CLINICAL FEATURES:
Treatment :

 Estrogen administration along with calcium supplementation


in combination with vitamin D to postmenopausal women
reduces the risk of fractures.

 Higher dietary intake of Ca (about 1.5 g/day) is recommended


for elderly people.
PHOSPHORUS(P).
 An adult body contains about 1 kg phosphate and it is
found in every cell of the body. About 80% occurs in
combination with Ca in the bones and teeth.
 About 10% of body Phosphorus is found in muscles and
blood.
 The remaining 10% is widely distributed in various
chemical compounds.

Phosphorus Distribution

10%
Bones and Teeth
10% Blood and Muscles
Remaining

80%
BIOCHEMICAL FUNCTION OF PHOSPHORUS:

1. Phosphorus is essential for the development of bones and


teeth.

2. It plays a central role for the formation and utilization of


high-energy phosphate compounds e.g. ATP, GTP, creatine
phosphate etc.

3. Phosphorus is required for the formation of phospholipids,


phosphoproteins and nucleic acids (DNA and RNA).
4. It is an essential component of several nucleotide
coenzymes.
e.g. NADP+, pyridoxal phosphate, ADP, AMP.

5. Several proteins and enzymes are activated by


phosphorylation.

6. Phosphate buffer system is important for the maintenance


of pH in the blood as well as in the cells.
DIETARY REQUIREMENTS:
 The recommended dietary allowance (RDA) of phosphate
is based on the intake of calcium.
 The ratio of Ca : P of 1:1 is recommended (i.e. 800
mg/day) for an adult. For infants, however, the ratio is
around 2 :1, which is based on the ratio found in human
milk.
 Ca:P ratio in most of the food is 1:1. So adequate calcium
rich food takes care of Phosphorus too.
SOURCES:
Milk, cereals, leafy vegetables, meat, eggs.

P
ABSORPTION:
Phosphate absorption occurs from jejunum.

FACTORS AFFECTING PHOSPHATE ABSORPTION:

 Calcitriol promotes phosphate uptake along with calcium.


 Absorption of phosphorus and calcium is optimum when
the dietary Ca : P is between 1:2 and 2:1

 Acidity favours while phytate decreases phosphate uptake


by intestinal cells.
SERUM PHOSPHATE:
 The phosphate level of the whole blood is around 40 mg/dl
while serum contains about 3- 4 mg/dl.
 This is because the RBC and WBC have very high content of
phosphate.

Existence of serum phosphate


Protein bound
10%

Complex form
50%
Free form
40%
EXCRETION:

 About 500 mg phosphate is excreted in urine per day.

 The renal threshold is 2 mg/dl.

 The reabsorption of phosphate by renal tubules is inhibited by PTH.


DISEASE STATES

 Serum phosphate level is increased in hypoparathyroidism


and decreased in hyperparathyroidism.

 In severe renal diseases, serum phosphate content is


elevated causing acidosis.

 Vitamin D deficient rickets is characterized by decreased


serum phosphate (1-2 mg/dl).
 Renal rickets is associated with low serum phosphate
levels and increased alkaline phosphatase activity.

 In diabetes mellitus, serum content of organic phosphate


is lower while that of inorganic phosphate is higher.
CONCLUSION
 Calcium and phosphorous plays a major role in
development of oral structures including tooth,
periodontium and alveolar bone.

 It also helps in maintaining the equilibrium of human


body.
REFERENCES:
 Essentials of biochemistry by Satyanarayana 3rd edition.
 Essentials of biochemistry by Vasudevan 8th edition.
 Lehninger Principles OF BIOCHEMISTRY 7th edition.
 Dr. Manu Rathee, Dr. Shefali Singla, Dr. Amit Kumar
Tamrakar Calcium and Oral Health: A Review
International Journal of Scientific Research, Vol : 2,
Issue : 9 September 2013
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